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| June 2012 Volume 8, Issue 6 | | | | | Focus Editorial Commentary Research Highlights News and Views Reviews Articles | | Advertisement | | | | Looking to keep pace with global news and research in the chemical sciences? Join RSC e-membership today to receive a digital subscription to Chemistry World, the unrivalled monthly magazine with an international readership of 49,000 scientists. Access the latest developments in research and government policy, business news, features and opinion columns, jobs board, and networking opportunities. | |
| | | | | | Advertisement | | The nature.com open innovation pavilion now has several research and development Challenges in genetics, molecular cell biology, chemistry, physics, immunology and more! Submit your solution to any of our Challenges for a chance to win cash awards ranging from $5,000 to $1M. Visit the pavilion or become a Solver today! | | | | Focus | Top | | | | Metabolism in 3D Metabolism is reemerging as a central topic in chemistry and biology, and chemical biologists are poised to improve our understanding of complex questions such as regulation, flux, and spatial organization. In this issue, we feature reviews and commentary outlining the recent advances and outstanding challenges in metabolism research. Metabolism in 3D | | Editorial | Top | | | | Beyond blueprints p495 doi:10.1038/nchembio.997 Renewed interest in the biological significance and applied outcomes of metabolism is moving the field from static biochemical charts to multidimensional networks. Full Text | PDF | | Commentary | Top | | | | Teaching the design principles of metabolism pp497 - 501 Joshua D Rabinowitz and Livia Vastag doi:10.1038/nchembio.969 Learning metabolism inevitably involves memorizing pathways. The teacher's challenge is to motivate memorization and to help students progress beyond it. To this end, students should be taught a few fundamental chemical reaction mechanisms and how these are repeatedly used to achieve pathway goals. Pathway knowledge should then be reinforced through quantitative problems that emphasize the relevance of metabolism to bioengineering and medicine. Full Text | PDF | | Research Highlights | Top | | | | Metabolic engineering: Assembling activity | RNA transport: An hnRNP ruler | Stem cells: Imatinib gets beta | Neurobiology: Smells like mitochondria | Chemical probes: Motor control | Metabolism: Lathosterone for longer life | Biosynthesis: Malonyl? Stet. | Cell biology: Peroxisomes come together | News and Views | Top | | | | | | Reviews | Top | | | | Rethinking glycolysis: on the biochemical logic of metabolic pathways pp509 - 517 Arren Bar-Even, Avi Flamholz, Elad Noor and Ron Milo doi:10.1038/nchembio.971 Abstract | Full Text | PDF | | | | Engineering synthetic recursive pathways to generate non-natural small molecules pp518 - 526 Elizabeth A Felnagle, Asha Chaubey, Elizabeth L Noey, Kendall N Houk and James C Liao doi:10.1038/nchembio.959 Abstract | Full Text | PDF | | | | Natural strategies for the spatial optimization of metabolism in synthetic biology pp527 - 535 Christina M Agapakis, Patrick M Boyle and Pamela A Silver doi:10.1038/nchembio.975 Abstract | Full Text | PDF | | | | Systems metabolic engineering of microorganisms for natural and non-natural chemicals pp536 - 546 Jeong Wook Lee, Dokyun Na, Jong Myoung Park, Joungmin Lee, Sol Choi and Sang Yup Lee doi:10.1038/nchembio.970 Abstract | Full Text | PDF | | Articles | Top | | | | Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ and p53 signaling pp547 - 554 Mathew Sajish, Quansheng Zhou, Shuji Kishi, Delgado M Valdez Jr, Mili Kapoor, Min Guo, Sunhee Lee, Sunghoon Kim, Xiang-Lei Yang and Paul Schimmel doi:10.1038/nchembio.937
Trp-tRNA synthetase (TrpRS) has a well-understood role in translation by facilitating aminoacylation of Trp-tRNAs. The discovery of a nuclear signaling role for TrpRS as a bridging protein for DNA-PK and PARP-1, resulting in p53 activation, explains a previously curious link between interferon-γ signaling and concomitant TrpRS overexpression. Abstract | Full Text | PDF |
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| | | | Synthetic oligonucleotides recruit ILF2/3 to RNA transcripts to modulate splicing pp555 - 561 Frank Rigo, Yimin Hua, Seung J Chun, Thazha P Prakash, Adrian R Krainer and C Frank Bennett doi:10.1038/nchembio.939
Antisense oligonucleotides (ASOs) are widely used to modulate gene expression through sequence-specific duplex formation with target RNAs. ASOs containing specific 2′-fluorine substitutions are shown to recruit ILF2/3 to pre-mRNA and induce exon skipping in cells and in mice. Abstract | Full Text | PDF See also: News and Views by Eperon |
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| | | | Ultrasensitive regulation of anapleurosis via allosteric activation of PEP carboxylase pp562 - 568 Yi-Fan Xu, Daniel Amador-Noguez, Marshall Louis Reaves, Xiao-Jiang Feng and Joshua D Rabinowitz doi:10.1038/nchembio.941
Bacteria must control their metabolism to quickly adapt to changing carbon sources. PEP carboxylase is now shown to be allosterically regulated by fructose-1,6-bisphosphate in an ultrasensitive manner, turning glycolysis on and off almost instantaneously in response to glucose availability. Abstract | Full Text | PDF |
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| | | | YcaO domains use ATP to activate amide backbones during peptide cyclodehydrations pp569 - 575 Kyle L Dunbar, Joel O Melby and Douglas A Mitchell doi:10.1038/nchembio.944
Cyclodehydrations in thiazole/oxazole-modified microcin biosynthesis are known to require a multiprotein complex, but full details of the reaction were not clear. Substrate analogs and isotopic labeling now show the D protein, thought to serve a scaffolding function, catalyzes ring formation and uses ATP to activate the substrate. Abstract | Full Text | PDF See also: News and Views by Kelly |
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| | | | A selective inhibitor reveals PI3Kγ dependence of TH17 cell differentiation pp576 - 582 Giovanna Bergamini, Kathryn Bell, Satoko Shimamura, Thilo Werner, Andrew Cansfield, Katrin Müller, Jessica Perrin, Christina Rau, Katie Ellard, Carsten Hopf, Carola Doce, Daniel Leggate, Raffaella Mangano, Toby Mathieson, Alison O'Mahony, Ivan Plavec, Faiza Rharbaoui, Friedrich Reinhard, Mikhail M Savitski, Nigel Ramsden, Emilio Hirsch, Gerard Drewes, Oliver Rausch, Marcus Bantscheff and Gitte Neubauer doi:10.1038/nchembio.957
A chemoproteomic approach adapted for high-throughput screening leads to the identification of a selective PI3Kγ inhibitor. Application of this inhibitor in human and mouse cellular models reveals a role for PI3Kγ in TH17 cell differentiation. Abstract | Full Text | PDF | Chemical compounds |
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| | | | Fluorescent castasterone reveals BRI1 signaling from the plasma membrane pp583 - 589 Niloufer G Irani, Simone Di Rubbo, Evelien Mylle, Jos Van den Begin, Joanna Schneider-Pizoń, Jaroslava Hniliková, Miroslav Šíša, Dieter Buyst, Josep Vilarrasa-Blasi, Anna-Mária Szatmári, Daniël Van Damme, Kiril Mishev, Mirela-Corina Codreanu, Ladislav Kohout, Miroslav Strnad, Ana I Caño-Delgado, Jiří Friml, Annemieke Madder and Eugenia Russinova doi:10.1038/nchembio.958
Brassinosteroids (BRs) are plant growth hormones that bind the brassinosteroid receptor (BRI1) and activate its kinase domain. Exploration of BRI1-BR trafficking using a fluorescent brassinosteroid probe alongside chemical and genetic tools reveals that endocytosis pathways are essential for BR signaling attenuation and BRI1 turnover. Abstract | Full Text | PDF | Chemical compounds |
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| | | | Domain organization differences explain Bcr-Abl's preference for CrkL over CrkII pp590 - 596 Wojciech Jankowski, Tamjeed Saleh, Ming-Tao Pai, Ganapathy Sriram, Raymond B Birge and Charalampos G Kalodimos doi:10.1038/nchembio.954
NMR structures of CrkL, an adaptor protein that mediates Bcr-Abl signaling in CML, reveal domain organization distinct from CrkII that allows constitutive interaction between CrkL and Abl kinase. Abstract | Full Text | PDF See also: News and Views by Kobashigawa & Inagaki |
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